Automated sampling method for medical diagnostic instrument

ABSTRACT

A novel fluid sampling device has been developed. This device provides for sample entry to be handled automatically by the instrument, thus allowing the operator to be involved in other activities while the sampling process is underway. It also assures reproduceable sample size, automatically cleans the sampling device between samples, and reduces the risk of user injury. Furthermore, the sampling system allows for the use of any forseeable collection mechanism.

This is a continuation of copending application Ser. No. 07/891,553,filed on May 29, 1992.

BACKGROUND

This invention relates to a device which is used for sampling fluidswhich are to be analyzed by a laboratory instrument. Although manyapplications are contemplated, the one used to describe the operation ofthe device is for analysis of sampled blood. The blood is normallycollected by using a syringe to draw the blood or by collecting theblood in a glass capillary tube.

The currently available analytical instruments use three methods ofdelivering the blood sample to the instrument. First, if a syringe isused, the sample might be injected into the instrument sampling port.There is much variability in this approach, due to the fact that (1) theforce used to inject the sample may vary from operator to operator, (2)the force used to inject the sample into the instrument may vary fromtest to test, (3) the force may vary throughout the injection of asingle sample, and (4) the sample size may vary from test to test.

Second, some instruments aspirate the sample from the syringe. For theseinstruments to be operable, a sampling probe protruding from theinstrument must be manually aligned with the syringe carrying the blood.This approach takes much time, demands manual dexterity on the part ofthe user, requires cleaning the probe after each use to avoidcross-contamination of samples, risks skin puncture of the technician bythe probe, and risks exposure of the technician to blood overflow.

Third, if the sample is introduced via a capillary, it is necessary insome instruments to attach a special adaptor to the capillary so thatthe sample can be drawn from the capillary by a vacuum drawn by theinstrument. This requires time to connect the adaptor, risks exposure ofthe technician to potentially contaminated blood, and requires manualcleaning or disposal of equipment, including the adaptor. In someinstruments the operator is forced to hold and maintain a seal with thesample entry throughout the aspiration process.

SUMMARY OF THE INVENTION

A novel fluid sampling device has been developed. This device providesfor sample entry to be handled automatically by the instrument, thusallowing the operator to be involved in other activities (such asmonitoring other instruments, etc.) while the sampling process isunderway. It also assures reproduceable sample size, automaticallycleans the sampling device between samples, and reduces the risk of userinjury from innoculation by the probe. Furthermore, the sampling systemallows for the use of any forseeable collection mechanism.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 represents the sampling device during the process of drawing asample from a syringe.

FIG. 2 represents the sampling device drawing a sample from a capillary.

FIG. 3 represents the front view of the "smart door" system.

FIG. 4 represents the side view of the "smart door" system.

FIG. 5 represents the probe obstruction detection system.

FIG. 6 represents the wash system.

FIG. 7 represents the foam generation system.

DETAILS OF THE INVENTION

A novel sampling device, intended primarily for use in handling bloodsamples to be analyzed in medical diagnostics instruments, has beendeveloped. This sampling device also has utility in other applicationswhere liquid, gaseous, solid or mixed-phase (e.g., suspensions, such asblood or plasma) samples are drawn. Examples of other instruments wherethe device could show utility include analytical chemistry instruments,air sampling and analysis instruments, food sampling instruments, etc.

For the purpose of this invention, the mechanism involved in sensing thetype of container holding the sample, drawing the sample from thecontainer, cleaning the portions of the mechanism exposed to sample, andrelated activities is referred to collectively as the device. Portionsof the device are referred to as systems. The entire mechanism,including the "device" and the portion which analyzes the sample drawn,is referred to as the instrument.

The main attributes of the sampling device are that:

1. sampling is handled automatically so that the operator can be freedto perform other tasks while the sampling is taking place,

2. samples can be drawn from a variety of container types,

3. a reproduceable sample size is drawn (including a reproduceable rateof drawing the sample),

4. the sampling device is automatically and effectively washed aftereach sample is drawn, and

5. user safety is improved.

FIG. 1 shows a schematic of the sampling device with a syringe as thesample holder. 1 represents the "smart door", 2 represents the sampleentry Luer, 3 is the inlet for the wash solution, 4 is the outlet forpumped waste, 5 is the probe, and 6 is the gas and reagent port (wherestandardizing gas and liquid samples are drawn into the instrument andoverflow sample is allowed to escape). 17 represents the capillary sealthrough which the probe is moved and which forms a seal with the probe.It also creates a seal with the inserted capillary. 18 represents theprobe obstruction detection system, to be discussed further in referenceto FIG. 5, and 19 represents the linear bidirectional actuator, whichmoves the probe into a syringe.

The sample entry Luer is tapered using the ANSI/HIMA MD70.1-1983standard taper that is used on all syringes, and contains the gas andreagent port referred to above (item 6). The syringe, without itsneedle, is held tightly by friction against the female Luer taper, andthe sampling device automatically draws the sample, thus freeing thetechnician to perform other tasks while the sampling takes place.

The Luer can be made of any material that will hold the syringe in thedesired orientation and will not contaminate the sample, for examplepolyethylene, stainless steel, silicone, urethane, TEFLON(polytetrofuoroethylene), and preferably clear acrylic, for examplePOLYCAST (polymethylmethacrylate) by Rohm and Haas, or PERSPEX(methacrylic acid) made by ICI. The acrylic PMMA(polymethylmethacrylate) has the added benefit of making the Luertransparent. All standard types of syringes will fit into the Luer,although it is most likely that syringes holding between 1 cc and 30 ccwill be used.

It should be noted that capillaries that are used to collect bloodsamples will also fit into the sample entry system and the preferredembodiment is one in which the capillary will be firmly held in ahorizontal position in the capillary seal. (See FIG. 2, where item 25represents the capillary.) The capillary seal is designed to have aconical shape in order to hold all the different capillary sizes. Thecapillary seal can be made of any material that is flexible enough tohold and seal the capillary and the sample probe. The material must alsonot contaminate the sample. For example, thermoset rubbers, such assilicon (for example, GE 4404 43-50 shore A durometer), andthermoplastic rubbers, such as KRAYTON (SBR Rubber) G or D (from Shell),can be used. Because of the capillary seal design, all forseeablediameters of capillaries can be used, although the most common areexpected to be between 50 and 175 μl volume.

The materials discussed above hold the syringe, capillary or othersample container in the Luer or capillary seal primarily by frictionalforces between the sample container and the Luer. Alternatively, amaterial or design that does not cause the sample container to be heldby friction can be used, but in that case a different mechanism forholding the sample container in the Luer must be included.

It should also be noted that, due to the uniformly tapered design of thesample entry system (Luer or capillary seal), the sample container(syringe, capillary, or other container) is held rigidly in the centerof the Luer and aligned concentrically with the narrow-opening end ofthe Luer.

When the syringe or capillary is positioned in the sample entry system,the operator presses the start switch, and the "smart door" closes byrotating about the pivot point connecting it to the device. This "smartdoor" is actually a moving arm which determines the type of containerpresent by measuring the diameter thereof. The location where it stopsits motion is an indicator to the device of the type of blood holdingcontainer that is being used.

The type of sample container detected indicates to the instrument how asample is to be drawn from the sampling device. If a syringe isdetected, a movable probe is inserted into the syringe to draw, in areproduceable manner, using vacuum applied to the probe, the sample ofblood from the container of blood. If a capillary is detected, a vacuum,applied to the probe in a reproduceable manner, draws the sample fromthe capillary. Because of the low vacuum used in the sampling pump,there is little chance that a clot will get into and clog theinstrument.

After the instrument draws the sample from the syringe or other sampleholder, the user is instructed to remove the sample holder, at whichtime the door automatically closes, blocking the Luer entry. While entryof a sample is prevented, the instrument performs the operations ofanalyzing the previously drawn sample, washing the Luer and samplingprobe, and calibrating the instrument.

Analytical instruments currently in the marketplace provide for sampleentry "straight ahead" into the instrument (i.e., the syringe orcapillary points along a line going from the operator). Unexpectedly, ithas been found that it is easier to utilize the novel device if there isa sidewise orientation of the sampling system, particularly if it ispointing towards the right side, when the user is facing the instrument.Not only has it been found easier for right-handed persons to use, butalso, because of the ease of aligning the sample container with theLuer, it has also been found easier for left-handed persons to use.Furthermore, because the syringe (or other sample holder) no longerextends towards the operator, but rather along the instrument or over a"guard" that can easily be designed into the instrument, the syringe andsample are less likely to be accidentally jarred by the operator andknocked from the instrument.

The integration of all of the systems of the device contribute to thereduction of risk to the instrument's operator, due both to thereduction in risk of injury and in reduction in the exposure to blood.Specifically, the probe does not operate until the smart door firstdetects a sample collection device (i.e., syringe, capillary, etc.)inserted in the Luer; due to the ability of the probe to detectobstructions, the likelihood of its puncturing skin is negligible; theentire sampling takes place in a closed area, reducing spillage,backsplash and exposure to blood; and automatic washing of the systembetween samples reduces exposure due to contamination from sampleresidues.

Detailed descriptions of the systems referred to above follow.

Smart Door Operation

The Smart Door Assembly is shown in FIGS. 3 (front view) and 4 (sideview). The door, 1, is coupled to a shaft, 7, that pivots about acontact point and rotates via a stepper motor, 8. The door shaft has adrive piece, 9, and a driven piece, 10. The drive piece is directlycoupled to the stepper motor. The driven piece is connected (via aspring coupling) to the drive piece, and it includes the door and theoptical detector, 11, for determining the stopping point for the flag,12, on the driven piece, which has the same movement as the door.

Two locations for the door are fixed in the instrument's memory: thehome, or fully opened, location and the fully closed location, and thesepositions are established by optical position detectors. Other locationsfor common types of syringes and capillaries are also programmed in theinstrument. When the door is closing, the stepper motor counts thenumber of steps that the shaft has taken from its home position until itintercepts the sampling device. The point of interception is determinedwhen the optical detector, 11, is tripped.

Unusual sampling devices, for example special sizes of syringes andcapillaries, can be programmed into the instrument by the user.

For example, the following data might represent the table of steps forseveral sampling devices:

    ______________________________________                                        Position/Container                                                                            Number of Steps                                               ______________________________________                                        Door open       0                                                             30 cc syringe   25-30                                                         12 cc syringe   39-40                                                         3 cc syringe    79-80                                                         2 cc syringe    89-90                                                         1 cc syringe    98-99                                                         275 μl capillary                                                                           114-115                                                       100 μl capillary                                                                           133-134                                                       Door closed     175                                                           ______________________________________                                    

Motorized Probe Operation

A probe that has a sufficiently small outside diameter (typically from0.032-0.046 in.) so that it can fit into the various syringes beingused, is employed to draw sample in a reproduceable fashion from thesyringes. The sample probe can be made of metal (e.g., stainless steel,titanium or inconel) or plastic (e.g., PEEK (polyetheretherketone) (ICIAmerica), KEL-F (Cholorotrifluoroethylene) (3M), etc.). Once the systemdetects, via the use of the "smart door", that a syringe is present, theprobe is activated. The motorized probe is automatically advancedthrough the capillary seal into the syringe barrel and the sample isdrawn into the instrument. Alternatively, the probe can remainstationary, and the syringe and Luer can move laterally until the probeis inside the syringe. When the capillary is the sample container, avacuum system is connected to the capillary for withdrawing an aliquotof sample.

The motorized probe has the ability to sense a small obstruction at theprobe tip, for example a syringe plunger, a finger, etc. As small aforce as 0.25 pounds can be detected, which is less than what would beencountered in hitting intact skin. As a result, the device minimizesthe chance of injuring a technician. In addition, the device adapts thesampling procedure to the volume of sample in the container, assuringthat air will not be drawn into the instrument along with the sample. Ifthe probe encounters an obstruction during its outward motion, it sensesthe obstruction, stops its forward motion, retracts, and the instrumentdisplays a probe obstruction message to the user. If the systemdetermines that too small of a sample is present, the probe will bewithdrawn, and an error message will be displayed. If the instrumentshould fail to detect a problem and proceeds with sampling, twodetectors in the sampling line assure that there is present an integralsample (i.e., the detectors determine if a bubble exists in the sampleline, using, for example, a conductivity or optical measuring device).If a problem with the sample is detected, an error message is displayed.

The Probe Obstruction Detection System is shown in FIG. 5. The method ofdetecting the obstruction utilizes an optical detector, 13, a flag, 14,mounted on a cantilever flex beam, 15, and a push rod, 16 that is incontact with the flex beam. As the probe encounters an obstruction, theprobe pushes on the push rod, the flex beam bends and the flaginterrupts the optical detector's light path. By adjusting theelectronic signal processing, the obstruction detection sensitivity canbe increased or decreased.

Device Cleaning

The device senses when a sample or reference has been drawn andinitiates the washing cycle after each material (sample or reference)has been drawn. During this washing cycle the probe, capillary conicalseal, and related components are automatically cleaned to avoidcontamination. It should be noted that, during each cleaning operation,the smart door is automatically closed in order to prevent theintroduction of a new sample. The wash and waste fluidic paths residewithin the Luer. (See. FIG. 6.) The wash solution, which contains asurfactant, such as BRIJ (Polyroxyethylene) (from ICI) or TRITON X100(octoxynal-9) (from Rohm and Haas), is introduced in the Luer inlet, 3,which is directly above the probe's outside surface, while the probe islocated in the Luer/probe wash position (see FIG. 6). The wash solutionfills the Luer and capillary seal, and it surrounds the outside of theprobe. The outside area of the probe that is surrounded with the foamwash solution is the area that was inserted into the syringe and thusrequires washing.) The waste is collected in the Luer at the probe'soutside bottom surface, 4. The outside of the probe exposed to the bloodsample is washed inside the Luer without the probe coming in contactwith any parts of the instrument. Once the outside of the probe iswashed, the probe is withdrawn into the capillary seal, 17, where thewashing of the capillary seal and interior of the probe takes place. Thewashing cycle takes place at the same time that the instrument'smeasurement cycle occurs, in order to optimize instrument throughput. Inaddition to the cleaning provided by the washing solution, cleaning alsooccurs by the wiping of the outside of the probe by the narrowestportion of the capillary seal (26) when the probe is withdrawn into itshome position, which is the reagent/gas/wash entry location (6). Thenarrowest portion of the capillary also provides a seal with the probe.(It should be noted that cleaning of the balance of the instrument thatis exposed to sample or calibration solution is separately conductedafter each such material is drawn through the instrument.)

In the preferred embodiment, even though the Smart Door does not make aseal with the Luer port, wash solution does not leak because of theproperties of the foam wash solution (surface tension, etc.). Inaddition, the timing of the peristaltic pump, which delivers the washsolution, and the waste pump are synchronized so that there will be noexcess wash solution to drip out of the Luer. Alternatively, the SmartDoor could make contact with the Luer port, especially if a washsolution having other properties (e.g., a solution containing an organicsolvent) were used.

The generation and delivery of foam wash into the Luer is the techniqueused to wash and clean the blood from the outside of the probe and theinside of the Luer. The generation of foam in a controlled manner hasbeen found to provide cleaning in a reliable, simple and effectivemanner. It has been found to be more efficient, due to the fluid volumeconsumption and drip minimization, than systems currently used by otherinstruments, which involve either immersing the probe into a wash bathor manual washing of the sampling probe. In addition, the techniquesused in other instruments require either expensive hardware or manualintervention.

The foam wash (see FIG. 7) is developed by having two different insidediameter size tubes (pump tubes) on a peristaltic pump, 20. Thedifference in the inside diameter of the tubing is required to obtain anoptimum flow rate ratio of surfactant to water. The smaller diametertube, 21, pushes wash solution into a "T" junction, 22, where the largertube, 23, pulls air in front of the "T" junction. The liquid and airform a mixture in this "T" junction. The size of the air to liquidmicrosegments can be varied by changing the tubing diameters. The largerdiameter tube also delivers the air/liquid mixture via the wash solutioninlet (3) into the Luer, where they become foam (i.e., form a foamstructure). In order to generate in the Luer foam of the desired bubblesize for the preferred embodiment, the liquid segments should be smallerthan 5 μl in volume and preferably about 1μl in volume. The foam washand waste are delivered to the waste reservoir (24 in FIG. 1) from theLuer by vacuum generated by a waste pump. Variations in the foamgeneration system are contemplated as a means of expanding theusefulness of the device. For example, it would be possible to increasethe number of tubes and, therefore, utilize this system to mixcomponents and create a foam from a multicomponent solution.

The above descriptions of the device and systems are not intended tolimit their usefulness, and those with ordinary skill in the art will beable to envision variations which are consistent with the intended usethereof. For example, the device can be used to draw suspensions such asliquid food samples, gas samples analyzed for occupational healthmonitoring, etc. These samples can then be delivered to the appropriateanalytical system.

What is claimed is:
 1. A method for sampling material which is heldwithin a container said method comprising:inserting said container intothe large end of an inwardly tapered bore on a holder, detecting thepresence and diameter of the container of said material, said containerbeing one of a syringe and a capillary, comparing the diameter to astored data base to determine whether the container is a syringe or acapillary, and if a syringe what the volume is, withdrawing a sample ofsaid material, wherein said withdrawing is controlled in response to thepresence and diameter of said container, said withdrawingcomprising,when the container is a syringe, inserting a sampling probethrough the small end of said holder bore into said syringe to a depthdetermined by the volume of said syringe, followed by applying a vacuumto said probe to withdraw the sample therethrough, when the container isa capillary, applying a vacuum to a sampling probe, said sampling probehaving been inserted into the small end of the holder bore, and cleaningsaid holder bore and probe exposed to said material between thewithdrawal of subsequent samples, using a cleaning solution, saidcleaning comprising,generating reproducible air-liquid microsegmentsusing a T junction connecting an air inlet with at least two pump tubes,a first one of which carries a wash solution and a second one whichcarries air for the liquid microsegments, allowing the microsegmentscarried by the second tube to form an air-liquid reproducible mixture,and allowing the air-liquid mixture to form a foam wash in said bore. 2.A method for sampling material which is held within a container saidmethod comprising,detecting the identity and diameter of a container ofsaid material, said container being one or a syringe and capillary, saidmethod for detecting comprising,positioning the container into thelarger end of an inwardly tapered bore of a holder, rotating an armaround a pivot point adjacent said holder, and determining an amount ofrotation of said arm, said amount of rotation determining the identityand diameter of said container, comparing said diameter to a stored database to determine whether the container is a syringe of a capillary andif a syringe, what the volume is, withdrawing a sample of said materialby inserting a probe into said container and sucking said material fromsaid container through said probe, wherein said inserting is controlledin response to the identity and diameter of said container, said probebeing constructed and arranged to sense the presence of, and avoidobstructions in its path, said probe comprising, a flag mounted on aflexible cantilevered beam and a push rod in contact with the flexiblebeam attached to said probe, and an optical detector for detecting theflag whereby,if a syringe is detected, said probe is inserted into saidsyringe through the small end of said holder bore to a depth determinedby the volume of the syringe, if a capillary is detected, said probe isinserted into the small end of said holder bore, and cleaning saidholder bore and probe exposed to said material between the withdrawal ofsubsequent sample, using a cleaning solution.
 3. A device for samplingbiological materials within a container held by frictional forces in thedevice comprising,a holder bore having an inwardly tapered boretherethrough for receipt of a container through the large end of thebore, a rotating arm for detecting the identity and diameter of acontainer of a material adjacent to the holder, a means for detectingthe rotation of said arm and comparing to a data base to determine theidentity of the container, a sampling probe adjacent the small end ofsaid bore and means for inserting said probe into the bore forwithdrawing a sample of the material, wherein said insertion means iscontrolled in response to the identity and diameter of said container,said probe being constructed and arranged to sense the presence of, andavoid obstructions in its path, said probe comprising a flag mounted ona flexible cantilevered beam, a push rod in contact with the flexiblebeam attached to said probe, and an optical detector for detecting theflag, and a means for cleaning said holder bore and probe exposed to thematerial between the withdrawal of subsequent samples wherein a cleaningsolution is contained within the cleaning means.